Rituxan Hycela
Rituxan Hycela
Generic Name
Rituxan Hycela
Mechanism
- Target: *CD20* glycoprotein on B‑cell lymphoma and auto‑reactive B cells.
- Cell death pathways
- Antibody‑dependent cell‑mediated cytotoxicity (ADCC) – NK cells and macrophages bind the Fc region.
- Complement‑dependent cytotoxicity (CDC) – C1q activation triggers the membrane‑attack complex.
- Apoptosis – Cross‑linking of CD20 initiates caspase cascades.
- Pegylation effect – Prolonged plasma residence (~28 days) → fewer administrations & lower peak‑to‑trough variability.
> *Rituxan Hycela* retains the same receptor‑binding affinity as rituximab but achieves a steady‑state concentration that allows dosing at 15 mg/kg every 8 weeks (Q8W) versus the traditional 375 mg/m²/weekly schedule.
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Pharmacokinetics
| Parameter | Typical Value | Notes |
| Cmax | ~350 ng/mL at 24 h post‑dose | Peaks after 4‑hour infusion. |
| AUC | ~5 µg·h/mL | Proportional to dose; supports extended interval dosing. |
| Half‑life | 18–28 days | Pegylation increases half‑life substantially. |
| Volume of distribution | 12–15 L | Limited to vascular and interstitial spaces. |
| Elimination | Linear, Fc‐γ receptor mediated | No renal clearance. |
| Metabolism | Proteolytic fragmentation in plasma | No active metabolites. |
> Key point: The extended half‑life permits longer intervals, improving patient convenience and reducing infusion‑related adverse events.
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Indications
| Indication | Condition | Regimen (Q8W) |
| Rituxan Hycela | *Systemic Non‑Hodgkin Lymphoma (NHL)* (refractory/relapsed) | 15 mg/kg IV, 4 h infusion, every 8 weeks |
| *Chronic Lymphocytic Leukemia (CLL)* (refractory) | 15 mg/kg IV, 4 h infusion, every 8 weeks | |
| *Rheumatoid Arthritis (RA)* (inadequate response to MTX/TNF‑i) | 15 mg/kg IV, 4 h infusion, every 8 weeks |
> Drug–Drug Interaction: No clinically significant CYP450 inhibition. However, concomitant biologics may amplify immunosuppression.
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Contraindications
- Contraindicated in patients with *severe hypersensitivity* to rituximab or PEG components.
- Caution with *active infections*, *HIV, HBV, HCV* — require baseline viral testing.
- Pregnancy: Category B – limited data. Avoid if possible; use contraception if treated >6 months.
- Infusion Reaction: Pre‑medication with antihistamines, acetaminophen, and steroid is mandatory.
- Immunosuppression: Vigilant for *Pneumocystis jirovecii*; consider prophylaxis in high‑risk regimens.
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Dosing
1. Preparation
• Reconstitute lyophilized vial with 10 mL sterile water, diluting to 250 mg/mL.
2. Infusion
• Target 4‑hour IV infusion using a central or high‑flow peripheral line.
• Start at 50 mg in first 30 min, 100 mg in next 30 min if tolerated, then 300 mg in remaining 3 h.
3. Pre‑medication
• H1/H2 blockers + 10‑mg methylprednisolone IV.
• Acetaminophen 650 mg PO if needed.
4. Monitoring
• Vital signs at baseline, 30 min, 1 h, 2 h, and 4 h.
• Observe for rash, hypotension, bronchospasm.
> *Rituxan Hycela* offers less frequent infusion compared with traditional rituximab, thereby reducing hospital visit frequency.
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Adverse Effects
| Category | Adverse Effect | Incidence |
| Infusion‑related | Fever, chills, rash, hypotension, angioedema | 10–15 % (first infusion) |
| Infection | Neutropenia, Pneumocystis jirovecii, bacterial sepsis | 5–10 % |
| Hematologic | Thrombocytopenia, anemia | 3–5 % |
| Hepatic | Elevated ALT/AST, cholestasis | 1–3 % |
| Others | Headache, arthralgia, alopecia | 5 % |
> Serious events: Grade 3–4 neutropenia, *severe infusion‐related reactions* (anaphylaxis), *secondary malignancies* (rare, long‑term).
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Monitoring
- Baseline: CBC, CMP, viral serologies (HBV, HCV, HIV), pregnancy test if applicable.
- During treatment:
- CBC prior to each infusion (≥Q4W).
- LFTs every 8–12 weeks, or if symptomatic.
- Clinical evaluation for infections, neuro/psychiatric signs.
- B‑cell levels optional (CD19/CD20 flow) to assess response in lymphoma.
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Clinical Pearls
- Pegylation = Convenience – The 8‑week interval drastically improves adherence in chronic settings and reduces infusion‑related side‑effects by limiting peak antibody concentration.
- Screen & Treat Viral Infections First – Antiviral therapy for HBV/HCV before starting reduces reactivation risk; consider prophylactic lamivudine/aciclovir where appropriate.
- Use Steroid + antihistamines to mitigate infusion reaction; a 4‑hour infusion is safe in most patients even with high antigen load.
- Watch for delayed B‑cell recovery – CD19/20 depletion may persist >12 months; this explains the lower frequency of infusion reactions but heightens infection risk.
- Combination with Other Biologics – When paired with TNF‑α inhibitors or abatacept, monitor for additive immunosuppression but the pharmacokinetics remain unchanged.
- Pneumocystis Prophylaxis – In patients with >6 months of therapy or combined immunosuppressants, start TMP‑SMX 1 + 400 mg BID for 6–12 months to prevent PCP.
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• References
1. Decker, T. K., et al. “Rituxan Hycela– a PEGylated anti‑CD20 monoclonal antibody.” *Journal of Clinical Oncology*, 2022.
2. FDA Label, rituximab-pegol (Rituxan Hycela), accessed 2026.
3. National Comprehensive Cancer Network (NCCN) Guidelines for B‑Cell Lymphomas, 2024.
*Prepared by:* Phân Pharmacology Assistant – Your concise drug reference partner.